Evaluation of an ex-vivo neonatal extracorporeal membrane oxygenation circuit on antiepileptic drug sequestration

Perfusion ◽  
2021 ◽  
pp. 026765912110281
Author(s):  
Shamir N Kalaria ◽  
Omayma A Kishk ◽  
Mathangi Gopalakrishnan ◽  
Dayanand N Bagdure
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Antiepileptic Drug ◽  
Centrifugal Pump ◽  
Normal Saline ◽  
Whole Blood ◽  
Ex Vivo ◽  
Ecmo Circuit ◽  
Human Whole Blood ◽  
Membrane Oxygenation ◽  
Drug Sequestration

Antiepileptic dosing information used to manage neonatal patients receiving extracorporeal membrane oxygenation (ECMO) is limited. The objective of this study is to quantify the extent of sequestration of various antiepileptic drugs using an ex-vivo neonatal ECMO circuit. Two neonatal closed-loop ECMO circuits were prepared using a Rotaflow centrifugal pump, custom polyvinylchloride tubing and a Quadrox-i Neonatal membrane oxygenator. After 5 minutes of circuit priming and stabilization with normal saline/albumin or expired human whole blood, single boluses of levetiracetam (200 mg), lacosamide (20 mg), and phenytoin (200 mg) were injected into the circuit. To account for spontaneous drug degradation, two polyvinylchloride beakers were filled with normal saline/albumin or expired human whole blood and equivalent antiepileptic drug doses were prepared. Simultaneous pharmacokinetic samples were collected from the control solution and the pre-centrifugal pump, pre-oxygenator, and post-oxygenator sampling ports from each circuit. Similar drug recovery profiles were observed among the three sampling sites investigated. Percent drug sequestration after a 24-hour circuit flow period was relatively similar between the two different circuits and ranged between 5.5%–13.2% for levetiracetam, 18.4%–22.3% for lacosamide, and 24.5%–30.2% for phenytoin. A comparison at 12 and 24 hours demonstrated similar percent drug sequestration across all three drugs in each circuit. Percent drug sequestrations for levetiracetam and lacosamide were less than 20% and for phenytoin were as high as 30% based on the sampling following single bolus dose administration into a neonatal ECMO circuit. Careful consideration of patient clinical status should be taken in consideration when optimizing antiepileptic therapy in neonates receiving ECMO.

scholarly journals Effects of an Ex Vivo Pediatric Extracorporeal Membrane Oxygenation Circuit on the Sequestration of Mycophenolate Mofetil, Tacrolimus, Hydromorphone, and Fentanyl

2019 ◽  
Vol 24 (4) ◽  
pp. 290-295
Author(s):  
Catherine S. Heith ◽  
Lizbeth A. Hansen ◽  
Rhonda M. Bakken ◽  
Sharon L. Ritter ◽  
Breeanna R. Long ◽  
...  
Keyword(s):  
Mycophenolate Mofetil ◽  
Extracorporeal Membrane Oxygenation ◽  
Mycophenolic Acid ◽  
Pediatric Patients ◽  
Ex Vivo ◽  
Centrifugal Pumps ◽  
Ecmo Circuit ◽  
Binding Characteristics ◽  
Membrane Oxygenation ◽  
Set Up

OBJECTIVES With the expanding use of extracorporeal membrane oxygenation (ECMO), understanding drug pharmacokinetics has become increasingly important, particularly in pediatric patients. This ex vivo study examines the effect of a pediatric Quadrox-iD ECMO circuit on the sequestration and binding of mycophenolate mofetil (MMF), tacrolimus, and hydromorphone hydrochloride, which have not been extensively studied to date in pediatric ECMO circuits. Fentanyl, which has been well studied, was used as a comparator. METHODS ECMO circuits were set up using Quadrox-iD pediatric oxygenators and centrifugal pumps. The circuit was primed with whole blood and a reservoir was attached to represent a 5-kg patient. Fourteen French venous and 12 French arterial ECMO cannulas were inserted into the sealed reservoir. Temperature, pH, PO2, and PCO2 were monitored and corrected. MMF, tacrolimus, hydromorphone, and fentanyl were injected into the ECMO circuit. Serial blood samples were taken from a postoxygenator site at intervals over 12 hours, and levels were measured. RESULTS Hydromorphone hydrochloride was not as significantly sequestered by the ex vivo pediatric ECMO circuit when compared with fentanyl. Both mycophenolic acid and tacrolimus serum concentrations were stable in the circuit over 12 hours. CONCLUSIONS Hydromorphone may represent a useful medication for pain control for pediatric patients on ECMO due to its minimal sequestration. Mycophenolic acid and tacrolimus also did not show significant sequestration in the circuit, which was unexpected given their lipophilicity and protein-binding characteristics, but may provide insight into unexplored pharmacokinetics of particular medications in ECMO circuits.

Influence of Extracorporeal Membrane Oxygenation Circuit on Nutritional Supplements

2020 ◽  
Vol 3 (5) ◽  
pp. 01-09
Author(s):  
AS Thiara
Keyword(s):  
Vitamin A ◽  
Extracorporeal Membrane Oxygenation ◽  
Ex Vivo ◽  
Nutritional Supplements ◽  
Ecmo Support ◽  
Blood Pump ◽  
Ecmo Circuit ◽  
Membrane Oxygenation ◽  
Over Time ◽  
Control Samples

Background The main function of extracorporeal membrane oxygenation (ECMO) is to provide systemic perfusion and gas exchange for patients with severe, acute respiratory or cardiac illness. The ECMO system consists of blood pump and a membrane oxygenator. ECMO oxygenator fibers, blood pump and tubing may bind circulating compounds such as drugs and nutritional components during ECMO support. Any loss of vital nutrients due to adsorption to the ECMO circuits may lead to further nutritional debilitation in critical ill patients. Objective The purpose of study is to analyze the amount of nutritional supplements adsorbed to the ECMO circuit under controlled ex vivo conditions Methods Six identical ECMO circuits were primed with fresh human whole blood and maintained under physiological conditions at 36°C for 24 hours. A dose of nutritional supplement calculated for a 70 kg patient was added. 150 mL volume was drawn from priming bag for control samples and kept under similar conditions. Blood samples were obtained at predetermined time points and analyzed for concentrations of vitamins, minerals, lipids, and proteins. Statistical analyses were performed using mixed models with robust standard errors, which allows for repeated samples within each setup and incomplete data. Results No significant differences were found between the ECMO circuits and controls for any of the measured variables: cobalamin, folate, vitamin A, glucose, concentration of minerals, HDL cholesterol, LDL cholesterol, total cholesterol, triglycerides, and total proteins. There was an initial decrease and then and increase in the concentration of cobalamin and folate. Vitamin A concentrations decreased in both groups over time. There was a decrease in concentration of glucose and an increased concentration of lactate dehydrogenase over time in both groups. Conclusion There were no changes in the concentrations of nutritional supplements in an ex vivo ECMO circuit compared to control samples, indicating that parenteral nutrition can be given during ECMO support. However, the time span of this study was limited, and the design made it impossible to investigate any functional and structural changes over time in nutritional supplements which lead to diminished effects through the ECMO circuit.

Impact of ex-vivo extracorporeal membrane oxygenation circuitry on daptomycin

Perfusion ◽  
2018 ◽  
Vol 33 (8) ◽  
pp. 624-629 ◽  
Author(s):  
Jeffrey J. Cies ◽  
Wayne S. Moore ◽  
Nadji Giliam ◽  
Tracy Low ◽  
Adela Enache ◽  
...  
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Closed Loop ◽  
Ex Vivo ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Ecmo Circuit ◽  
Drug Degradation ◽  
Membrane Oxygenation ◽  
Apparent Volume Of Distribution ◽  
Larger Sample

Background: The objective was to determine the alterations of daptomycin (DAP) in a contemporary neonatal/pediatric (1/4-inch) and adolescent/adult (3/8-inch) extracorporeal membrane oxygenation (ECMO) circuit including the Quadrox-i® oxygenator. Methods: Quarter-inch and 3/8-inch, simulated, closed-loop, ECMO circuits were prepared with a Quadrox-i pediatric and Quadrox-i adult oxygenator and blood primed. A one-time dose of DAP was administered into the circuit and serial pre- and post-oxygenator concentrations were obtained at 0-5 minutes and 1, 2, 3, 4, 5, 6 and 24-hour time points. DAP was also maintained in a glass vial and samples were taken from the vial at the same time periods for control purposes to assess for spontaneous drug degradation Results: For both the 1/4-inch and 3/8-inch circuits, there was no significant DAP loss at 24 hours. Additionally, the reference DAP concentrations remained relatively constant during the entire 24-hour study period. Conclusion: This ex-vivo investigation demonstrated no significant DAP loss within an ECMO circuit with both sizes of the Quadrox-i oxygenator at 24 hours. Therapeutic concentrations of DAP in the setting of ECMO may be anticipated with current recommended doses, depending on the amount of extracorporeal volume needed for circuit maintenance in comparison to the patient’s apparent volume of distribution. Additional studies with a larger sample size are needed to confirm these findings.

Potential drug sequestration during extracorporeal membrane oxygenation: results from an ex vivo experiment

2007 ◽  
Vol 33 (6) ◽  
pp. 1018-1024 ◽  
Author(s):  
Nilesh M. Mehta ◽  
David R. Halwick ◽  
Brenda L. Dodson ◽  
John E. Thompson ◽  
John H. Arnold
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Ex Vivo ◽  
Potential Drug ◽  
Membrane Oxygenation ◽  
Drug Sequestration

scholarly journals Sedative and Analgesic Drug Sequestration After a Single Bolus Injection in an Ex Vivo Extracorporeal Membrane Oxygenation Infant Circuit

ASAIO Journal ◽  
2019 ◽  
Vol 65 (2) ◽  
pp. 187-191 ◽  
Author(s):  
Viviane G. Nasr ◽  
Jonathan Meserve ◽  
Luis M. Pereira ◽  
David Faraoni ◽  
Steve Brediger ◽  
...  
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Bolus Injection ◽  
Ex Vivo ◽  
Analgesic Drug ◽  
Single Bolus ◽  
Membrane Oxygenation ◽  
Drug Sequestration ◽  
Single Bolus Injection

Extracorporeal membrane oxygenation using a centrifugal pump and a servo regulator to prevent negative inlet pressure

1997 ◽  
Vol 63 (5) ◽  
pp. 1333-1339 ◽  
Author(s):  
Thore H. Pedersen ◽  
Vibeke Videm ◽  
Jan L. Svennevig ◽  
Harald Karlsen ◽  
Randi Wolden Østbakk ◽  
...  
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Centrifugal Pump ◽  
Inlet Pressure ◽  
Membrane Oxygenation

Adenosine Infusion Improves Oxygenation in Term Infants With Respiratory Failure

PEDIATRICS ◽  
1996 ◽  
Vol 97 (3) ◽  
pp. 295-300
Author(s):  
G. Ganesh Konduri ◽  
Daisy C. Garcia ◽  
Nadya J. Kazzi ◽  
Seetha Shankaran
Keyword(s):  
Pulmonary Hypertension ◽  
Placebo Group ◽  
Extracorporeal Membrane Oxygenation ◽  
Normal Saline ◽  
Medical Center ◽  
Blood Gases ◽  
Adenosine Infusion ◽  
Term Infants ◽  
Membrane Oxygenation ◽  
Arterial Blood

Objective. Adenosine infusion causes selective pulmonary vasodilation in fetal and neonatal lambs with pulmonary hypertension. We investigated the effects of a continuous infusion of adenosine on oxygenation in term infants with persistent pulmonary hypertension of newborn (PPHN). Design. A randomized, placebo-controlled, masked trial comparing the efficacy of intravenous infusion of adenosine to normal saline infusion over a 24-hour period. Setting. Inborn and outborn level III neonatal intensive care units at a university medical center. Participants. Eighteen term infants with PPHN and arterial postductal Po2 of 60 to 100 Torr on inspired O2 concentration of 100% and optimal hyperventilation (PaCo2 <30 Torr) were enrolled into the study. Study infants were randomly assigned to receive a placebo infusion of normal saline, or adenosine infusion in doses of 25 to 50 µg/kg/min over a 24-hour period. Results. Nine infants each received adenosine or placebo. The two groups did not differ in birth weight, gestational age, or blood gases and ventilator requirements at the time of entry into the study. Four of nine infants in the adenosine group and none of the placebo group had a significant improvement in oxygenation, defined as an increase in postductal PaO2 of ≥20 Torr from preinfusion baseline. The mean PaO2 in the adenosine group increased from 69 ± 19 at baseline to 94 ± 15 during 50 µg/kg/min infusion rate of adenosine and did not change significantly in the placebo group. Arterial blood pressure and heart rate did not change during the study in either group. The need for extracorporeal membrane oxygenation, incidence of bronchopulmonary dysplasia, and mortality were not different in the two groups. Conclusion. Data from this pilot study indicate that adenosine infusion at a dose of 50 µg/kg/min improves PaO2 in infants with PPHN without causing hypotension or tachycardia. Larger trials are needed to determine its effects on mortality and/or need for extracorporeal membrane oxygenation in infants with PPHN.

A Case Report of Combat Blast Injury Requiring Combat Casualty Care, Far-Forward ECMO, Air Transport, and All Levels of Military Critical Care

2021 ◽  
Author(s):  
Lydia C Piper ◽  
Jason J Nam ◽  
John P Kuckelman ◽  
Valerie G Sams ◽  
Jeffry D DellaVolpe ◽  
...  
Keyword(s):  
Critical Care ◽  
Extracorporeal Membrane Oxygenation ◽  
Whole Blood ◽  
Operative Management ◽  
Blast Injury ◽  
Esophageal Injury ◽  
Resuscitative Thoracotomy ◽  
Membrane Oxygenation ◽  
Combat Casualty ◽  
Cord Injury

ABSTRACT We describe a 34-year-old soldier who sustained a blast injury in Syria resulting in tracheal 5 cm tracheal loss, cervical spine and cord injury with tetraplegia, multiple bilateral rib fractures, esophageal injury, traumatic brain injury, globe evisceration, and multiple extremity soft tissue and musculoskeletal injuries including a left tibia fracture with compartment syndrome. An emergent intubation of the transected trachea was performed in the field, and the patient was resuscitated with whole blood prehospital. During transport to the Role 2, the patient required cardiopulmonary resuscitation for cardiac arrest. On arrival, he underwent a resuscitative thoracotomy and received a massive transfusion exclusively with whole blood. A specialized critical care team transported the patient to the Role 3 hospital in Baghdad, and the DoD extracorporeal membrane oxygenation (ECMO) team was activated secondary to his unstable airway and severe hypoxia secondary to pulmonary blast injury. The casualty was cannulated in Baghdad approximately 40 hours after injury with bifemoral cannulae in a venovenous configuration. He was transported from Iraq to the U.S. Army Institute of Surgical Research Burn Center in San Antonio without issue. Extracorporeal membrane oxygenation support was successfully weaned, and he was decannulated on ECMO day 4. The early and en route use of venovenous ECMO allowed for maintenance of respiratory support during transport and bridge to operative management and demonstrates the feasibility of prolonged ECMO transport in critically ill combat casualties.

scholarly journals Surface modification of decellularized bovine carotid arteries with human vascular cells significantly reduces their thrombogenicity

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Eriselda Keshi ◽  
Peter Tang ◽  
Marie Weinhart ◽  
Hannah Everwien ◽  
Simon Moosburner ◽  
...  
Keyword(s):  
Surface Modification ◽  
Whole Blood ◽  
Carotid Arteries ◽  
Complete Blood Count ◽  
Ex Vivo ◽  
Vascular Grafts ◽  
Blood Perfusion ◽  
Vascular Cells ◽  
Perfusion System ◽  
Human Whole Blood

Abstract Background Since autologous veins are unavailable when needed in more than 20% of cases in vascular surgery, the production of personalized biological vascular grafts for implantation has become crucial. Surface modification of decellularized xenogeneic grafts with vascular cells to achieve physiological luminal coverage and eventually thromboresistance is an important prerequisite for implantation. However, ex vivo thrombogenicity testing remains a neglected area in the field of tissue engineering of vascular grafts due to a multifold of reasons. Methods After seeding decellularized bovine carotid arteries with human endothelial progenitor cells and umbilical cord-derived mesenchymal stem cells, luminal endothelial cell coverage (LECC) was correlated with glucose and lactate levels on the cell supernatant. Then a closed loop whole blood perfusion system was designed. Recellularized grafts with a LECC > 50% and decellularized vascular grafts were perfused with human whole blood for 2 h. Hemolysis and complete blood count evaluation was performed on an hourly basis, followed by histological and immunohistochemical analysis. Results While whole blood perfusion of decellularized grafts significantly reduced platelet counts, platelet depletion from blood resulting from binding to re-endothelialized grafts was insignificant (p = 0.7284). Moreover, macroscopic evaluation revealed thrombus formation only in the lumen of unseeded grafts and histological characterization revealed lack of CD41 positive platelets in recellularized grafts, thus confirming their thromboresistance. Conclusion In the present study we were able to demonstrate the effect of surface modification of vascular grafts in their thromboresistance in an ex vivo whole blood perfusion system. To our knowledge, this is the first study to expose engineered vascular grafts to human whole blood, recirculating at high flow rates, immediately after seeding.

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